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XB-ART-39261
Pflugers Arch 2008 Oct 01;4571:223-31. doi: 10.1007/s00424-008-0489-2.
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Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias.

Hagos Y , Krick W , Braulke T , Mühlhausen C , Burckhardt G , Burckhardt BC .


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Glutaric acidurias are rare inherited neurodegenerative disorders accompanied by accumulation of the metabolites glutarate (GA) and 3-hydroxyglutarate (3OHGA), glutaconate, L: -, or D: -2-hydroxyglutarate (L: -2OHGA, D: -2OHGA) in all body fluids. Oocytes expressing the human (h) sodium-dicarboxylate cotransporter (NaDC3) showed sodium-dependent inward currents mediated by GA, 3OHGA, L: -, and D: -2OHGA. The organic anion transporters (OATs) were examined as additional transporters for GA derivatives. The uptake of [(3)H]p-aminohippurate in hOAT1-transfected human embryonic kidney (HEK293) cells was inhibited by GA, 3OHGA, D: -, or L: -2OHGA in a concentration-dependent manner. None of these compounds affected the hOAT3-mediated uptake of [(3)H]estrone sulfate (ES). In hOAT4-expressing cells and oocytes, ES uptake was strongly increased by intracellular GA derivatives. The data provide a model for the concerted action of OAT1 and NaDC3 mediating the basolateral uptake, and OAT4 mediating apical secretion of GA derivatives from proximal tubule cells and therefore contribute to the renal clearance of these compounds.

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Species referenced: Xenopus laevis
Genes referenced: kcnk3 slc13a3 slc22a6

References [+] :
Alebouyeh, Expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites. 2003, Pubmed